ZMIZ2-MCM3 axis participates in the progression of triple-negative breast cancer

Objective: Triple-negative breast cancer (TNBC) is highly aggressive in nature and lacks effective targeted therapies. This study aimed to elucidate the function and possible mechanisms of ZMIZ2 and MCM3 in TNBC progression.Methods: The relationship between ZMIZ2 expression and clinical characteristics of TNBC was investigated. The in vitro and in vivo experiments were employed to study the role of ZMIZ2 dysregulation on TNBC cell malignant behaviors. The regulatory relationship between ZMIZ2 and MCM3 was explored. Furthermore, transcriptome sequencing was carried out to elucidate the possible mechanisms of ZMIZ2/MCM3 axis in TNBC.Results: High ZMIZ2 expression is linked to the malignant degree of TNBC. ZMIZ2 overexpression promoted TNBC cell proliferation, migration, and invasion, inhibited apoptosis, and induced S phase cell cycle arrest, whereas knockdown of ZMIZ2 had opposite effects. ZMIZ2 directly targeted and positively regulated MCM3 expression. MCM3 knockdown reversed the function of ZMIZ2 overexpression on TNBC tumor growth in vitro and in vivo. High MCM3 expression was linked to the malignant degree and poor prognosis of TNBC. The differentially expressed genes associated with ZMIZ2/MCM3 axis were significantly enriched in multiple pathways, such as MAPK, mTOR, Wnty, and Ras signaling pathways, which were verified by TCGA data.Conclusions: ZMIZ2 and MCM3 are increased expressed in TNBC. ZMIZ2 promotes the development of TNBC through positively regulating MCM3. Key pathways, such as Ras/MAPK, PI3K/AKT/mTOR, and Wnt signaling pathways may be key downstream mechanisms.